Kidney Recipients Research Articles

Association of Donor Vascular Endothelial Growth Factor Gene Polymorphism With Acute Renal Allograft Rejection.

Recipient's VEGF-A polymorphisms have been reported to be associated with the risk of acute allograft rejection. However, an association of the donor's VEGF-A gene polymorphism with rejection remained unelucidated till now. In this study, VEGF-A gene SNPs at nine loci were analyzed in 160 kidney donors and recipients with rejection (rejectors, n=80) and without rejection (non-rejectors, n=80). Blood VEGF-A mRNA, plasma VEGF level, and intragraft VEGF expression were also analyzed by RT-PCR, ELISA, and immunohistochemistry, respectively. On comparing between the donor and rejectors, the polymorphic genotypes of VEGF -634 C>G [GG genotype, p<0.0001; OR (95% CI) = 17.74 (5.16-60.96)]; VEGF -1154 G>A [AG genotype, p<0.0001, OR (95% CI)=16.07 (3.68-70.15)]; VEGF +936 C>T [CT genotype, p<0.0001, OR (95% CI)=178.64 (23.28-1370.9), and TT genotype, p<0.0001; OR (95% CI)=3149 (278.91-35553)]; VEGF -1455 T>C [CC genotype, p value=0.0464, OR (95% CI) = 3.13 (1.07-9.10)]; VEGF -2578 C>A [CA genotype, p=0.0426, OR (95% CI)=4.62 (1.03-20.59), and AA genotype, p value<0.0001, OR (95% CI) = 21.89 (4.94-97.04)]; VEGF -2549 18bp Insertion/Deletion [ID genotype, p value<0.0001, OR (95% CI)=27.27 (3.61-205.73) and DD genotype, p value<0.0001, OR (95% CI)=25.18 (3.30-191.89) were significantly associated with acute rejection risk. On comparing rejectors versus non-rejectors, GA genotype of VEGF -1190 G>A and TC genotype of VEGF -1455 T>C were associated with the risk of rejection. On comparing donor VEGF between rejectors and non-rejectors, CG genotype of VEGF -634 C>G, AG of VEGF -1154 G>A; GA of VEGF -1190 G>A were associated with rejection. The blood VEGF-A mRNA and plasma VEGF levels were higher in the rejectors group compared to non-rejectors. Besides the recipient's VEGF SNPS, the donor's VEGF SNPs are also associated with the risk of acute rejection and may be closely monitored in evaluation to determine the risk of rejection.

Posttransplant Lymphoproliferative Disorder in Pediatric Solid-Organ Transplant Recipients: A 7-Year Single-Center Analysis.

Posttransplant lymphoproliferative disorder is a consequential complication following solid-organ transplant, particularly associated with the Epstein-Barr virus. We studied a single center's cases of pediatric posttransplant lymphoproliferative disorder for a 7-year period and focused on incidence rates, anatomic sites involved, and correlation with clinical outcomes. We explored clinical features and treatment outcomes in patients with pediatric posttransplant lymphoproliferative disorder, with emphasis on patient survival and associated clinical ramifications. This was a retrospective analysis of medical records from pediatric solid-organ transplant recipients (liver or kidney) at Baskent University Ankara Hospital Organ Transplantation Center between January 1, 2017, and January 1, 2024, approved by the Institutional Review Board (KA24/63). We identified cases based on pathology-confirmed persistent lymphadenopathy or tumorous lesions. Patient categorization distinguished between malignant and benign groups. Early posttransplant lymphoproliferative disorder was defined within the initial year after transplant. Epstein?Barr virus association was determined through in situ hybridization, and patient characteristics were reviewed comprehensively. In 7 years, 10 pediatric patients (9 liver transplants, 1 kidney transplant) were diagnosed with posttransplant lymphoproliferative disorder, with an incidence of 8.7% for pediatric liver transplants. Mean age at diagnosis was 46.4 months, and mean time from transplant to diagnosis was 21.2 months. The most common complaints at diagnosis included fever, lymphadenopathy, hepatosplenomegaly, dyspnea, and diarrhea. Treatment modalities included rituximab, immunosuppression reduction, intravenous immunoglobulin therapy, and chemotherapy (NHL Berlin-Frankfurt-Münster 90 protocols). All patients achieved remission (mean follow-up, 22.9 mo). Early diagnosis of posttransplant lymphoproliferative disorder is important, and rituximab with immunosuppression reduction is effective to achieve complete remission, particularly in early polymorphic cases. Despite challenges, all patients achieved remission, signaling improved outcomes in pediatric posttransplant lymphoproliferative disorder. Active monitoring of Epstein?Barr virus infection may further reduce posttransplant lymphoproliferative disorder complications in pediatric solid-organ transplant; hence, early diagnosis is crucial.

Urinary Metabolite Constellation Also Detects Very Early Post-transplant Rejection in Living Donor Kidney Recipients

Urinary Metabolite Constellation Also Detects Very Early Post-transplant Rejection in Living Donor Kidney Recipients

Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients.

Long-term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single-stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. TTV-based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long-term patient and graft survival. Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High-TTV load and high immunosuppression are associated with a risk of infection, and low-TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner etal. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV-guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation.

Antecedent Cardiac Arrest Status of Donation After Circulatory Determination of Death (DCDD) Kidney Donors and the Risk of Delayed Graft Function After Kidney Transplantation: A Cohort Study.

The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF). Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF. A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF. This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest.

Rare cases of primarily infected kidney graft transplantation with the development of purulent complications

Background. Unexpected transmission of an infectious disease agent with a kidney graft to a recipient is a rare event but it is associated with significant morbidity and mortality, especially when exposed to multidrug-resistant bacteria that have not been eliminated by standard antibiotic prophylaxis.Objective. To demonstrate the need for immediate removal of a primary infected kidney graft in the event of local purulent complications due to the rapid development of sepsis in immunocompromised patients.Results. The paper describes a clinical course of the infectious process in two kidney recipients each of whom underwent transplantation of a primary infected graft from a single donor, taking into consideration the transplantectomy timing and the treatment outcomes.Conclusion. The Case Report shows the need for immediate transplantectomy in a kidney graft recipient when local purulent complications are detected with confirmed primary infection of the graft due to a high risk of the rapid development of sepsis and threat to life.

Impact of New-Onset Diabetes after Transplantation on Cardiovascular Risk and Mortality in Korea: A Nationwide Population-Based Study.

Limited data are available on the adverse effects of new-onset diabetes after transplantation (NODAT) in solid organ transplantation (TPL) other than kidney. This study aimed to identify the risk of complications associated with NODAT in recipients of kidney, liver, or heart TPL. Using the Korean National Health Insurance Service database, recipients of kidney, liver, or heart TPL between 2009 and 2015 were identified. The incidence of coronary artery disease (CAD), cerebrovascular accident (CVA), and malignancy was compared across groups with NODAT, pretransplant diabetes mellitus (DM), and without DM using Cox regression analysis. A total of 9,632 kidney, liver, or heart TPL recipients were included. During the median follow-up of 5.9 years, NODAT independently increased the incidence of CAD (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.39 to 4.30) and overall mortality (HR, 1.48; 95% CI, 1.14 to 1.95) compared to the reference group even after adjustment for confounders; this was more prominent in kidney TPL than in liver TPL. The risk of CVA was significantly increased by pretransplant DM but not by NODAT in both kidney and liver TPL (HR, 2.47; 95% CI, 1.68 to 3.65; and HR, 3.18; 95% CI, 1.07 to 9.48, respectively). NODAT increased the risk of malignancy in the crude model, which lost its statistical significance after confounder adjustment. NODAT independently increases the risk of CAD and mortality after TPL, which is more evident in kidney recipients. There was no additional increased risk of CVA or malignancy with NODAT in solid organ TPL.

Belatacept Versus Tacrolimus for Kidney Transplant Recipients of Deceased Donors With Acute Kidney Injury: US National Database Study.

It is unclear whether kidney grafts from deceased donors with acute kidney injury (AKI) are more vulnerable to calcineurin inhibitor nephrotoxicity, and whether de novo use of belatacept is more beneficial than tacrolimus for recipients of these types of kidney transplants. In this retrospective cohort study using the US Organ Procurement and Transplantation Network database, we created 1:4 matches with highly similar characteristics for recipients of AKI-donor kidneys receiving belatacept versus tacrolimus for initial maintenance immunosuppression and compared outcomes for graft function, patient and graft survival, and rejection. The matched cohort consisted of 567 and 2268 recipients administered belatacept and tacrolimus, respectively. Posttransplant estimated glomerular filtration rate was significantly higher in the belatacept group at 6 mo (58.2 ± 24.2 versus 54.6 ± 21.6 mL/min/1.73 m2, P < 0.001); however, the between-group difference did not reach statistical significance at 12 mo (57.2 ± 24.3 versus 55.7 ± 22.2 mL/min/1.73 m2, P = 0.057). Median follow-up periods were 3.2 and 3.1 y for patient and graft survival, respectively. There were no significant differences between belatacept versus tacrolimus for mortality (hazard ratio 1.18 [95% confidence interval, 0.95-1.47], P = 0.14) or death-censored graft failure (hazard ratio 1.17 [0.85-1.61], P = 0.33). Rejection rate within 12 mo was significantly higher in the belatacept group (13% versus 7%, P < 0.001). In this matched cohort study, initial use of belatacept for AKI-donor kidney recipients was associated with small benefits in early graft function when compared with tacrolimus. Although rejection risk was significantly higher in recipients administered belatacept, patient and graft survival were not significantly different between groups.

Nitrofurantoin as an Add-On to Conventional Prophylaxis for the Treatment of Urinary Tract Infections in Kidney Recipients: A Prospective Cohort Study.

Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3-20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment.

249.7: Machine learning in transplant medicine: Predicting diarrheic diseases in kidney recipients.

249.7: Machine learning in transplant medicine: Predicting diarrheic diseases in kidney recipients.

P.209: One year pathological and clinical outcomes of recipients of donor exchange kidneys.

P.209: One year pathological and clinical outcomes of recipients of donor exchange kidneys.

447.3: Consistent rejection-free survival in baboon recipients of 10-gene edit pig donor kidneys with intensified anti-CD154 treatment: Intermediate-term results.

447.3: Consistent rejection-free survival in baboon recipients of 10-gene edit pig donor kidneys with intensified anti-CD154 treatment: Intermediate-term results.

P.164: Comparable graft survival of re-transplantation in elderly kidney recipients in regard to rejection.

P.164: Comparable graft survival of re-transplantation in elderly kidney recipients in regard to rejection.

P.173: The impact of post-transplant non-HLA antibody burden on the occurrence of antibody-mediated rejection and graft loss in non-sensitized pediatric kidney recipients.

P.173: The impact of post-transplant non-HLA antibody burden on the occurrence of antibody-mediated rejection and graft loss in non-sensitized pediatric kidney recipients.

Safety of Adjuvanted Recombinant Herpes Zoster Virus Vaccination in Fragile Populations: An Observational Real-Life Study.

Vaccination is the most effective strategy for preventing infectious diseases and related complications, and proving its efficacy is crucial for its success and adherence, especially for newly introduced vaccines, such as adjuvanted recombinant herpes zoster virus vaccination (RZV). In this observational real-life study, we recorded adverse effects following immunization (AEFIs) after RZV administration in frail populations. A total of 271 subjects underwent RZV at Vaccination Center, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy. Most subjects were solid organ transplant recipients (kidney, 77.1%; liver, 4.8%). Demographics, clinical data, and AEFIs (type, duration, and medications used) were recorded. Overall, 37% of participants reported at least one AEFI following the first dose, predominantly pain at the injection site (60%), while 41% did so after the second dose (pain at the injection site in 62% of cases). Medications were more frequently used for AEFI treatment after the second dose (28%) rather than after the first dose (13%) (p = 0.01). After stratification by sex, females experienced AEFIs more frequently than males, particularly local skin reactions. Our study added evidence of safety and tolerability of the adjuvanted recombinant RZV in frail adults.

Kidney Transplant Outcomes in Amyloidosis: US National Database Study.

We aimed to assess contemporary transplant outcomes among kidney recipients with amyloidosis, as the treatment and prognosis of amyloidosis have shown improvement over time. Using the US Organ Procurement and Transplantation Network database, we initially evaluated the changes in patient and graft survival among kidney recipients with amyloidosis from 2002 to 2021. We then compared transplant outcomes between recipients with amyloidosis versus those with diabetic and nondiabetic causes of kidney failure, creating 1:4 matches with highly similar characteristics separately for deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) during the last decade (2012-2021). We identified 643 kidney recipients with amyloidosis during 2002-2021. Patient and death-censored graft survival improved over time. In the matching analysis for 207 DDKT and 166 LDKT recipients with amyloidosis during 2012-2021, patient survival was not significantly different between amyloidosis and diabetes groups in both DDKT (log-rank, P = 0.057) and LDKT (P = 0.99). Compared with the nondiabetes group, patient survival in the amyloidosis group was not significantly different for DDKTs (P = 0.56) but was significantly lower for LDKTs (P = 0.04). Death-censored graft failure risk was not significantly different between amyloidosis and diabetes or nondiabetes groups for both DDKTs (P = 0.78 and 0.75) and LDKTs (P = 0.40 and 0.24). In this well-matched cohort study, we found no significant differences in patient and graft survival between kidney recipients with amyloidosis and those with diabetes. Similarly, these outcomes were not significantly different between those with amyloidosis versus nondiabetic causes, except for patient survival of LDKT recipients.

Efficacy of novel drugs hypoxia inducible factor prolyl hydroxylase inhibitor in therapy of posttransplant anemia. A review

Introduction The aim of our study was to evaluate the efficacy of novel drugs from the group of hypoxia-inducible factor prolyl hydroxylase inhibitors, using roxadustat as an example, in the treatment of anemia occurring in kidney recipients. In the study, we included data from recent original papers that examined the efficacy of these drugs in the treatment of post-transplant anemia. We assumed an absolute increase in hemoglobin concentration as a factor expressing the effectiveness of the therapy. Aim of the study The aim of our study was to evaluate the efficacy of novel drugs from the group of hypoxia-inducible factor prolyl hydroxylase inhibitors, using roxadustat as an example, in the treatment of anemia occurring in kidney recipients. In the study, we included data from recent original papers that examined the efficacy of these drugs in the treatment of post-transplant anemia. We assumed an absolute increase in hemoglobin concentration as a factor expressing the effectiveness of the therapy. Materials and Methods This review was conducted using publications available in databases such as PubMed, Google Scholar, Scopus and ScienceDirect. These databases were searched using keywords such as hypoxia-inducible factor prolyl hydroxylase inhibitor, roxadustat, anemia, kidney transplant, posttransplant anemia, chronic kidney disease. The time range of published articles was set to 2017-2024, and some older publications were included if they were considered to bring valuable background information necessary for understanding the issue. Articles written in English and Polish were sought; however, all publications used in this review were in English. The main reason of bias of this study may be the limited group of participants that may not be sufficiently representative, the lack of randomization in some studies, and the limited number of publications in the problem area.

Delayed peak antibody titers after the second dose of SARS-CoV-2 vaccine in solid organ transplant recipients: Prospective cohort study

Poor post-vaccination production of antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a concern among solid organ transplant (SOT) recipients. Furthermore, the timing and kinetics of antibody titers after the second vaccine dose are unknown. We conducted a multicenter prospective observational study that included 614 SOT recipients: 460 kidney, 53 heart, 50 liver, 20 lung, and 31 simultaneous pancreas–kidney (SPK). The participants received two doses of the mRNA vaccine (Pfizer BNT162b2 or Moderna mRNA-1273), as indicated. Serum samples were collected before the first and second vaccinations and at 1, 3, and 6 months after the second vaccine dose, which were then assessed for SARS-CoV-2 antibodies. The overall seropositivity rate was 43% at 1 month after administration of the second vaccine dose; it gradually increased to 68% at 3 months after second dose administration and to 70% at 6 months. In addition, recipient of kidney, lung or SPK transplants had lower antibody titers at the 3- and 6-month time points than did the other recipients. SOT recipients acquired SARS-CoV-2 S-IgG antibodies slowly, and the peak titer differed significantly from that of the general population.

Novel Potassium Binders for Early Postoperative Hyperkalemia in Kidney Transplant Recipients: A Single-Center Experience

PurposeEvaluate the safety/efficacy of novel potassium binders (patiromer, sodium zirconium cyclosilicate [SZ-9]) for early postoperative hyperkalemia following kidney transplantation. MethodsRetrospective, single-center, cohort study of deceased-donor kidney recipients transplanted between 1/2018 and 12/2020. Potassium-binder use was evaluated from immediately posttransplant until discharge. Potassium binders were administered ≥2 hours before/after medications. ResultsA total of 179 patients were included, 24 (13%) of whom received potassium binders (16 [67%] patiromer, 7 [29%] SZ-9, 1 [4%] both) for a mean of 2.5 (±3.18) doses. Peak potassium levels were higher in the potassium-binder group (6.05 vs 5.35 mEq/L; P < .001). More patients on potassium binders transitioned to atovaquone than those on no binders (n = 21 [100%] vs n = 112 [75%], respectively; P = .005). Delayed graft function (DGF) was observed in 100 (56%) patients, with a higher proportion receiving potassium binders (18 [75%] vs 82 [53%], respectively; P = .042). There was no difference between groups in number of posttransplant dialysis sessions required in the general study population (P = .2), nor in the DGF group (P = .12). No difference was noted in the incidence of ileus (P = .2), or gastrointestinal symptoms (diarrhea, nausea, vomiting; P = .6). Of the 24 patients who received inpatient binders, 9 (37.5%) were discharged and remained on them for a mean of 46 (±49) days. ConclusionPatiromer and SZ-9 appear safe in the early posttransplant period, but larger prospective trials are needed. Potassium-binder use does not appear to be associated with fewer dialysis sessions in DGF patients, however, they may be used as additional tools for lowering potassium in these patients.

Immunosuppression and transplantation-related characteristics affect the difference between eGFR equations based on creatinine compared to cystatin C in kidney transplant recipients.

Previous studies show heterogeneity when applying estimated glomerular filtration (eGFR) equations to kidney transplant recipients (KTRs). However, research on the impact of transplantation-related characteristics on eGFR equations using creatinine (eGFRcr) compared to cystatin C (eGFRcys) is scarce. We conducted a comprehensive analysis with three eGFRcr equations (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009, European Kidney Function Consortium (EKFC) 2021, kidney recipient specific-glomerular filtration rate KRS-GFR) 2023), comparing them to two eGFRcys (CKD-EPI 2012 and EKFC 2023) in 596 KTRs. Bland-Altman plots demonstrated relative differences according to different eGFR-stages. Multivariable logistic regression identified transplantation-related characteristics independently associated with smaller or greater differences between eGFRcr and eGFRcys equations. 94.3% of the cohort were White individuals. Median eGFR differed as much as 9ml/min/1.73 m2 between equations. The median relative differences (Q2) were greater (more negative) when comparing the eGFRcr equations to eGFRcys CKD-EPI 2012, than when comparing them to eGFRcys EKFC 2023 (P<.001). Better average eGFR was associated with smaller mean relative differences in all comparisons but eGFRcr CKD-EPI 2009 with eGFR EKFC 2023 and eGFRcr EKFC 2021 with eGFRcys EKFC 2023. Living kidney donation and belatacept use were independent factors associated with a smaller difference (≥Q3) between eGFRcr and eGFRcys equations, while prednisone use or higher HbA1c were independently associated with a greater difference (≤Q1) between equations. Different eGFR-stages, donor, or recipient characteristics, along with immunosuppression such as belatacept or prednisone, contribute to differences between eGFRcr and eGFRcys. These effects need to be considered in the clinical management of KTRs.